In recent years, our team at Iowa State University has found a way to make pigs an even closer stand-in for humans. We have successfully transferred components of the human immune system into pigs that lack a functional immune system. This breakthrough has the potential to accelerate medical research in many areas, including virus and vaccine research, as well as cancer and stem cell therapeutics.
Existing biomedical models
Severe Combined Immunodeficiency, or SCID, is a genetic condition that causes impaired development of the immune system. People can develop SCID, as dramatized in the 1976 movie “The Boy in the Plastic Bubble." Other animals can develop SCID, too, including mice.
Researchers in the 1980s recognized that SCID mice could be implanted with human immune cells for further study. Such mice are called “humanized" mice and have been optimized over the past 30 years to study many questions relevant to human health.
Mice are the most commonly used animal in biomedical research, but results from mice often do not translate well to human responses, thanks to differences in metabolism, size and divergent cell functions compared with people.
Nonhuman primates are also used for medical research and are certainly closer stand-ins for humans. But using them for this purpose raises numerous ethical considerations. With these concerns in mind, the National Institutes of Health retired most of its chimpanzees from biomedical research in 2013.
Alternative animal models are in demand.
Swine are a viable option for medical research because of their similarities to humans. And with their widespread commercial use, pigs are met with fewer ethical dilemmas than primates. Upwards of 100 million hogs are slaughtered each year for food in the U.S.
Humanizing pigs
In 2012, groups at Iowa State University and Kansas State University, including Jack Dekkers, an expert in animal breeding and genetics, and Raymond Rowland, a specialist in animal diseases, serendipitously discovered a naturally occurring genetic mutation in pigs that caused SCID. We wondered if we could develop these pigs to create a new biomedical model.
Our group has worked for nearly a decade developing and optimizing SCID pigs for applications in biomedical research. In 2018, we achieved a twofold milestone when working with animal physiologist Jason Ross and his lab. Together we developed a more immunocompromised pig than the original SCID pig – and successfully humanized it, by transferring cultured human immune stem cells into the livers of developing piglets.
During early fetal development, immune cells develop within the liver, providing an opportunity to introduce human cells. We inject human immune stem cells into fetal pig livers using ultrasound imaging as a guide. As the pig fetus develops, the injected human immune stem cells begin to differentiate – or change into other kinds of cells – and spread through the pig's body. Once SCID piglets are born, we can detect human immune cells in their blood, liver, spleen and thymus gland. This humanization is what makes them so valuable for testing new medical treatments.
We have found that human ovarian tumors survive and grow in SCID pigs, giving us an opportunity to study ovarian cancer in a new way. Similarly, because human skin survives on SCID pigs, scientists may be able to develop new treatments for skin burns. Other research possibilities are numerous.
The ultraclean SCID pig biocontainment facility in Ames, Iowa. Adeline Boettcher, CC BY-SA
Pigs in a bubble
Since our pigs lack essential components of their immune system, they are extremely susceptible to infection and require special housing to help reduce exposure to pathogens.
SCID pigs are raised in bubble biocontainment facilities. Positive pressure rooms, which maintain a higher air pressure than the surrounding environment to keep pathogens out, are coupled with highly filtered air and water. All personnel are required to wear full personal protective equipment. We typically have anywhere from two to 15 SCID pigs and breeding animals at a given time. (Our breeding animals do not have SCID, but they are genetic carriers of the mutation, so their offspring may have SCID.)
As with any animal research, ethical considerations are always front and center. All our protocols are approved by Iowa State University's Institutional Animal Care and Use Committee and are in accordance with The National Institutes of Health's Guide for the Care and Use of Laboratory Animals.
Every day, twice a day, our pigs are checked by expert caretakers who monitor their health status and provide engagement. We have veterinarians on call. If any pigs fall ill, and drug or antibiotic intervention does not improve their condition, the animals are humanely euthanized.
Our goal is to continue optimizing our humanized SCID pigs so they can be more readily available for stem cell therapy testing, as well as research in other areas, including cancer. We hope the development of the SCID pig model will pave the way for advancements in therapeutic testing, with the long-term goal of improving human patient outcomes.
Adeline Boettcher earned her research-based Ph.D. working on the SCID project in 2019.
Christopher Tuggle, Professor of Animal Science, Iowa State University and Adeline Boettcher, Technical Writer II, Iowa State University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
How can modern technology help warn us of impending volcanic eruptions?
One promising answer may lie in satellite imagery. In a recent study published in Nature Geoscience, researchers used infrared data collected by NASA satellites to study the conditions near volcanoes in the months and years before they erupted.
The results revealed a pattern: Prior to eruptions, an unusually large amount of heat had been escaping through soil near volcanoes. This diffusion of subterranean heat — which is a byproduct of "large-scale thermal unrest" — could potentially represent a warning sign of future eruptions.
For the study, the researchers conducted a statistical analysis of changes in surface temperature near volcanoes, using data collected over 16.5 years by NASA's Terra and Aqua satellites. The results showed that eruptions tended to occur around the time when surface temperatures near the volcanoes peaked.
Eruptions were preceded by "subtle but significant long-term (years), large-scale (tens of square kilometres) increases in their radiant heat flux (up to ~1 °C in median radiant temperature)," the researchers wrote. After eruptions, surface temperatures reliably decreased, though the cool-down period took longer for bigger eruptions.
"Volcanoes can experience thermal unrest for several years before eruption," the researchers wrote. "This thermal unrest is dominated by a large-scale phenomenon operating over extensive areas of volcanic edifices, can be an early indicator of volcanic reactivation, can increase prior to different types of eruption and can be tracked through a statistical analysis of little-processed (that is, radiance or radiant temperature) satellite-based remote sensing data with high temporal resolution."
Although using satellites to monitor thermal unrest wouldn't enable scientists to make hyper-specific eruption predictions (like predicting the exact day), it could significantly improve prediction efforts. Seismologists and volcanologists currently use a range of techniques to forecast eruptions, including monitoring for gas emissions, ground deformation, and changes to nearby water channels, to name a few.
Still, none of these techniques have proven completely reliable, both because of the science and the practical barriers (e.g. funding) standing in the way of large-scale monitoring. In 2014, for example, Japan's Mount Ontake suddenly erupted, killing 63 people. It was the nation's deadliest eruption in nearly a century.
In the study, the researchers found that surface temperatures near Mount Ontake had been increasing in the two years prior to the eruption. To date, no other monitoring method has detected "well-defined" warning signs for the 2014 disaster, the researchers noted.
The researchers hope satellite-based infrared monitoring techniques, combined with existing methods, can improve prediction efforts for volcanic eruptions. Volcanic eruptions have killed about 2,000 people since 2000.
"Our findings can open new horizons to better constrain magma–hydrothermal interaction processes, especially when integrated with other datasets, allowing us to explore the thermal budget of volcanoes and anticipate eruptions that are very difficult to forecast through other geophysical/geochemical methods."
Poverty can be a self-sustaining cycle that might require an external influence to break it. A new paper published in Nature Sustainability and written by professor Andrew Bell of Boston University suggests that we could improve global anti-poverty and economic development systems by turning to an idea in a video game about a race car-driving Italian plumber.
A primer on Mario Kart
For those who have not played it, Mario Kart is a racing game starring Super Mario and other characters from the video game franchise that bears his name. Players race around tracks collecting power-ups that can directly help them, such as mushrooms that speed up their karts, or slow down other players, such as heat-seeking turtle shells that momentarily crash other karts.
The game is well known for having a mechanism known as "rubber-banding." Racers in the front of the pack get wimpy power-ups, like banana peels to slip up other karts, while those toward the back get stronger ones, like golden mushrooms that provide extra long speed boosts. The effect of this is that those in the back are pushed towards the center, and those in front don't get any boosts that would make catching them impossible.
If you're in last, you might get the help you need to make a last-minute break for the lead. If you're in first, you have to be on the lookout for these breakouts (and the ever-dreaded blue shells). The game remains competitive and fun.
Rubber-banding: A moral and economic lesson from Mario Kart
In the real world, we see rubber-banding used all the time. Welfare systems tend to provide more aid to those who need it than those who do not. Many of them are financed by progressive taxation, which is heavier on the well-off than the down-and-out. Some research suggests that these do work, as countries with lower levels of income inequality have higher social mobility levels.
It is a little more difficult to use rubber-banding in real life than in a video game, of course. While in the game, it is easy to decide who is doing well and who is not, things can be a little more muddled in reality. Furthermore, while those in a racing game are necessarily antagonistic to each other, real systems often strive to improve conditions for everybody or to reach common goals.
As Bell points out, rubber-banding can also be used to encourage sustainable, growth programs that help the poor other than welfare. They point out projects such as irrigation systems in Pakistan or Payments for Ecosystems Services (PES) schemes in Malawi, which utilize positive feedback loops to both provide aid to the poor and promote stable systems that benefit everyone.
In the Malawi case, farmers were paid to practice conservation agriculture to reduce the amount of sediment from their farms flowing into a river. This immediately benefits hydroelectric producers and their customers but also provides real benefits to farmers in the long run as their soil doesn't erode. By providing an incentive to the farmers to conserve the soil, a virtuous cycle of conservation, soil improvement, and improved yields can begin.
While this loop differs from the rubber-banding in Mario, the game's approach can help illustrate the benefits of rubber-banding in achieving a more equitable world.
The task now, as Bell says in his paper, is to look at problems that exist and find out "what the golden mushroom might be."
